Delayed-onset, grade IV neutropenia associated with rituximab therapy in a lymphoma patient: A case report and literature review

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6682 Background: Several cases of delayed-onset (> 4 weeks post therapy) neutropenia associated with rituximab have been reported in lymphoma patients. The majority of patients have been heavily pre-treated with chemotherapy. This is the first report of delayed neutropenia in a patient receiving rituximab as part of first-line therapy. Methods: Delayed neutropenia and thrombocytopenia occurred in a 53-year old, male with high-grade B-cell lymphoma 6 weeks after completing 6 cycles of rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). The patient remains in complete remission 12 months after diagnosis. Six weeks after completing therapy, significant neutropenia and thrombocytopenia developed; WBC 700/mm3, neutrophil granulocytes 0.320/μL, PLT 71 x 103/μL. Complications included severe mucositis, oropharyngeal infections, weakness, weight loss, and fatigue. Treatment with filgrastim 480 μg daily improved neutrophil and platelet counts and controlled infections. However, discontinuation of filgrastim resulted in an ANC < 1000 and recurrent infections. Grade IV neutropenia developed 3 times. Full recovery occurred 5 to 7 days after filgrastim onset. The anti-neutrophil antibody was negative. A bone marrow biopsies during filgrastim therapy demonstrated hypercellularity (80%) and no abnormal leukocytes. The cytogenetic analysis showed normal karotypes. Pertinent history includes diffuse inflammatory lung disease during chemotherapy, which responded to steroids. Results: The neutropenia continues 6 months after completion of rituximab, but is controlled on 2 doses of filgrastim per week. Thrombocytopenia has resolved. Conclusions: Although Genentech reports the rate of delayed-onset neutropenia to be < 0.02%, a growing body of evidence suggests it is more common. Monitoring blood counts for up 8 weeks after rituximab therapy is worthwhile, although the literature reports neutropenia development 24 weeks post rituximab therapy. No significant financial relationships to disclose.